Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Khyber Pakhtunkhwa, Pakistan.
Department of Pharmacy, University of Malakand, Chakdara, Khyber Pakhtunkhwa, Pakistan.
Int J Nanomedicine. 2020 Nov 17;15:8999-9009. doi: 10.2147/IJN.S270746. eCollection 2020.
The aim of the studies was to fabricate aceclofenac (AC) tablets using nanosuspension as granulating fluid to boost its rate of in vitro dissolution and eventually its oral bioavailability.
The optimized nanosuspension with particle size of 112±2.01 nm was fabricated using HPMC 1% (w/v), PVP-K30 1% (w/v) and SLS 0.12% (w/v) at 400 watts of ultrasonication energy for 15 min duration and 3 sec pause. Then, the optimized aceclofenac nanosuspension was used as granulating fluid for aceclofenac tablets formulation. The characterization was performed using Malvern zetasizer, SEM, TEM, DSC and P-XRD. The granules were evaluated for the bulk and tapped densities, Hausner's ratio, angle of repose and their resulted values were found within limit. The prepared tablets were tested for average weight, hardness, friability, disintegration, dissolution and in vivo bioavailability in rabbits.
The in vitro dissolution data showed the boosted rate of nanosuspension-based tablets compared to the microsuspension-based tablets. The in vivo bioavailability (in rabbits model) of aceclofenac nanosuspension-based tablets (ACN-1, ACN-2) proved an improved absorption as in comparison to the marketed formulation. The C and AUC of ACN-1 and ACN-2 were 1.53-fold, 1.48-fold and 2.23-fold, 2.0-fold greater than that of the marketed drug, and were 1.74-fold, 1.68-fold and 2.3-fold, 2.21-fold greater in comparison to raw drug.
This boosted in vitro and in vivo bioavailability may be attributed to reduced particle size of aceclofenac nanoformulations used in tablets. Finally, this will result in faster absorption of these fabricated tablets.
本研究旨在通过将纳米混悬液用作造粒液来制备醋氯芬酸（AC）片剂，以提高其体外溶出率，最终提高其口服生物利用度。
采用 HPMC1%（w/v）、PVP-K301%（w/v）和 SLS0.12%（w/v），在 400 瓦超声能量下持续 15 分钟，每 3 秒暂停一次，制备粒径为 112±2.01nm 的优化纳米混悬液。然后，将优化的醋氯芬酸纳米混悬液用作醋氯芬酸片剂配方的造粒液。采用 Malvern 激光粒度仪、SEM、TEM、DSC 和 P-XRD 对其进行表征。对颗粒的堆密度、振实密度、Hausner 比、休止角进行评价，所得值均在限定范围内。对制备的片剂进行平均重量、硬度、脆碎度、崩解、溶出度和兔体内生物利用度的检测。
体外溶出数据表明，与基于微粉混悬液的片剂相比，纳米混悬液基片剂的溶出率提高。醋氯芬酸纳米混悬液基片剂（ACN-1、ACN-2）在兔体内的生物利用度（以兔模型为基础）证明了其吸收的改善，与市售制剂相比。ACN-1 和 ACN-2 的 C 和 AUC 分别是市售药物的 1.53 倍、1.48 倍和 2.23 倍、2.0 倍，分别是原料药的 1.74 倍、1.68 倍和 2.3 倍、2.21 倍。
这种体外和体内生物利用度的提高可能归因于片剂中使用的醋氯芬酸纳米制剂的粒径减小。最后，这将导致这些片剂更快地被吸收。
